Neuroprotective Effects of Opioid-Like Hibernation Factors in Cerebral Ischemia

The proposed study will help delineate the mechanism(s) by which opioid-like hibernation factors such as ZGI-04 and the hibernation induction trigger (HIT, 88kDa HRP) provide extended cerebral ischemic protection in mice. We hypothesize that the ischemic protection provided by these factors operates through mechanism(s) requiring activation of a delta opioid-receptor subtype. We hypothesize that the initial event in neuroprotection is meditated through KATPchannels and may involve activation of intermediates, which result in preservation, and/or enhancement of nitric oxide (NO) levels in ischemic tissue.